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Mutations in SLC26A1 Cause Nephrolithiasis

Lookup NU author(s): Professor John SayerORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Nephrolithiasis, a condition in which urinary supersaturation leads to stone formation in the urinary system, affects about 5%-10% of individuals worldwide at some point in their lifetime and results in significant medical costs and morbidity. To date, mutations in more than 30 genes have been described as being associated with nephrolithiasis, and these mutations explain about 15% of kidney stone cases, suggesting that additional nephrolithiasis-associated genes remain to be discovered. To identify additional genes whose mutations are linked to nephrolithiasis, we performed targeted next-generation sequencing of 18 hypothesized candidate genes in 348 unrelated individuals with kidney stones. We detected biallelic mutations in SLC26A1 (solute carrier family 26 member 1) in two unrelated individuals with calcium oxalate kidney stones. We show by immunofluorescence, immunoblotting, and glycosylation analysis that the variant protein mimicking p.Thr185Met has defects in protein folding or trafficking. In addition, by measuring anion exchange activity of SLC26A1, we demonstrate that all the identified mutations in SLC26A1 result in decreased transporter activity. Our data identify SLC26A1 mutations as causing a recessive Mendelian form of nephrolithiasis.

Publication metadata

Author(s): Gee HY, Jun I, Braun DA, Lawson JA, Halbritter J, Shril S, Nelson CP, Tan WZ, Stein D, Wassner AJ, Ferguson MA, Gucev Z, Sayer JA, Milosevic D, Baum M, Tasic V, Lee MG, Hildebrandt F

Publication type: Article

Publication status: Published

Journal: American Journal of Human Genetics

Year: 2016

Volume: 98

Issue: 6

Pages: 1228-1234

Print publication date: 02/06/2016

Online publication date: 19/05/2016

Acceptance date: 25/03/2016

Date deposited: 13/07/2016

ISSN (print): 0002-9297

ISSN (electronic): 1537-6605

Publisher: Cell Press


DOI: 10.1016/j.ajhg.2016.03.026


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Funder referenceFunder name
2013R1A3A2042197National Research Foundation of Korea, Ministry of Science, ICT and Future Planning
2015R1D1A1A01056685National Research Foundation of Korea, Ministry of Science, ICT and Future Planning
2015-32-0047Yonsei University College of Medicine
6-FY11-241March of Dimes Foundation